Pharmaceutical Industry Research Articles

Effects of alloferon and its analogues on reproduction and development of the Tenebrio molitor beetle

As the most numerous group of animals on Earth, insects are found in almost every ecosystem. Their useful role in the environment is priceless; however, for humans, their presence may be considered negative or even harmful. For years, people have been trying to control the number of pests by using synthetic insecticides, which eventually causes an increased level of resistance to applied compounds. The effects of synthetic insecticides have encouraged researchers to search for alternatives and thus develop safe compounds with high specificity. Using knowledge about the physiology of insects and the functionality of compounds of insect origin, a new class of bioinsecticides called peptidomimetics, which are appropriately modified insect analogues, was created. One promising compound that might be successfully modified is the thirteen amino acid peptide alloferon (HGVSGHGQHGVHG), which is obtained from the hemolymph of the blue blowfly Calliphora vicinia. Our research aimed to understand the physiological properties of alloferon and the activity of its peptidomimetics, which will provide the possibility of using alloferon or its analogues in the pharmaceutical industry, as a drug or adjuvant, or in agriculture as a bioinsecticide. We used alloferon and its three peptidomimetics, which are conjugates of the native peptide with three unsaturated fatty acids with various chain lengths: caprylic, myristic, and palmitic. We tested their effects on the morphology and activity of the reproductive system and the embryogenesis of the Tenebrio molitor beetle. We found that the tested compounds influenced the growth and maturation of ovaries and the expression level of the vitellogenin gene. The tested compounds also influenced the process of egg laying, embryogenesis, and offspring hatching, showing that alloferon might be a good peptide for the synthesis of effective bioinsecticides or biopharmaceuticals.

Genomic and Cell-Specific Regulation of Benzylisoquinoline Alkaloid Biosynthesis in Opium Poppy.

Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine and papaverine. Most enzymes involved in benzylisoquinoline alkaloids (BIAs) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition.

Graph Neural Networks for Predicting Solubility in Diverse Solvents Using MolMerger Incorporating Solute-Solvent Interactions.

The prediction of solubility is a complex and challenging physicochemical problem that has tremendous implications for the chemical and pharmaceutical industry. Recent advancements in machine learning methods have provided a great scope for predicting the reliable solubility of a large number of molecular systems. However, most of these methods rely on using physical properties obtained from experiments and expensive quantum chemical calculations. Here, we developed a method that utilizes a graphical representation of solute-solvent interactions using "MolMerger," which captures the strongest polar interactions between molecules using Gasteiger charges and creates a graph incorporating the true nature of the system. Using these graphs as input, a neural network learns the correlation between the structural properties of a molecule in the form of node embedding and its physicochemical properties as the output. This approach has been used to calculate molecular solubility by predicting the Log solubility values of various organic molecules and pharmaceuticals in diverse sets of solvents.

Determination of prebiotic activity and probiotic encapsulation ability of inulin type fructans obtained from Inula helenium roots.

Inulin, a prebiotic utilized in the food and pharmaceutical industries, promotes the growth of beneficial bacteria in the colon, thereby enhancing human health. Although inulin is commercially produced from chicory and artichoke, Inula helenium roots offer a high potential for inulin production. The aim of this study is to investigate the prebiotic activity of inulin (inulin-P) from I. helenium roots on Lactobacillus rhamnosus, as well as its ability to produce synbiotic microcapsules and the effects on probiotic viability during freeze-drying, in vitro gastrointestinal (GI) digestion, and storage. First, the effect of inulin-P on L. rhamnosus viability and short-chain fatty acid (SCFA) production was compared to other commonly utilized prebiotics. The findings revealed that inulin-P remarkably promoted the growth and SCFA yield of L. rhamnosus for 48h of fermentation and 28 days of storage. Then, L. rhamnosus was encapsulated with inulin-P and commercial inulin to compare its survival throughout storage and the GI tract. Inulin-P microcapsules outperformed in terms of viability during storage (7.98logCFU/g after 30 days at 4°C). Furthermore, inulin-P microcapsules were heat-resistant and protected L. rhamnosus from GI conditions, resulting in a high survival rate (89.52%) following large intestine simulation, which is ideal for increasing customer benefits. Additionally, inulin-P microcapsules exhibited similar physical characteristics to commercial inulin. Consequently, this study revealed that inulin-P, which is easy to produce, low-cost, and has industrial application potential, could be used as a good carrier for the synbiotic encapsulation of L. rhamnosus. PRACTICAL APPLICATION: Inulin is a prebiotic that promotes the activity and growth of beneficial bacteria in the human gut. Although commercial inulin is currently produced from chicory root and artichoke, Inula helenium root is a potential raw material for inulin production. In this study, inulin was produced from I. helenium roots with a low-cost and easy production method, and it was determined that this inulin was an effective carrier in the synbiotic encapsulation of L. rhamnosus. This inulin exhibits superior prebiotic activity and encapsulation efficiency compared to commercial inulins like Orafti® GR and HPX and can be easily integrated into industrial production.

Expression of the changes in essential oil components of Shirazi thyme (Zataria multiflora Boiss.) as affected by various drying methods

The purpose of this research was to investigate the impact of various drying techniques on the quality characteristics of Shirazi thyme (Zataria multiflora Boiss.) using a completely randomized design with three replications. The treatments included fresh samples, shade-drying (SHD), sun-drying (SD), oven and vacuum-drying (OD and VD) each at three different temperatures (45, 55, and 65 °C), and microwave-drying (MD) at three different power levels (200, 400, and 600 W). The results indicated that vacuum and oven-drying at 45 °C were effective in preserving valuable secondary metabolites compared to traditional drying methods. The essential oil (EO) content was lowest in the microwave-drying at 600 W (1.3 %), and highest in vacuum-drying at 45 °C (2.99 %). Vacuum-drying at 45 °C also produced the highest levels of carvacrol (72.5 %) and thymol (7.21 %) content, while the lowest levels were found in fresh samples. The main components in the EO were monoterpene hydrocarbons (11.47–27.33 %), oxygenated monoterpenes (74.81–86.9 %), and oxygenated sesquiterpenes (76.50–86.50 %). The results showed that the amount of sesquiterpene hydrocarbons and oxygenated monoterpenes were higher at low temperatures. Furthermore, the color parameters showed changes based on the drying methods, with vacuum-drying at 45 °C increasing the L* parameter (lightness), vacuum-drying at 65 °C increasing the a* parameter)brightness(, and oven-drying at 45 °C increasing the b* parameter)greenness). Understanding the different methods and operations of drying Shirazi thyme can provide valuable insight for its professional application and development in food and pharmaceutical industries.

Production of 5-fluorouracil-loaded PLGA nanoparticles with toroidal microfluidic system and optimization of process variables by design of experiments

In recent decades, microfluidics has presented new opportunities for the production of nanoparticles (NPs). However, to achieve rapid clinical translation, the production of PLGA NPs in a single microfluidic channel for both the pharmaceutical research and industry without the need for scaling is still limited. The aim of this study was to accomplish the production of reproducible and stable 5-FU loaded Poly(lactic-co-glycolic acid) (PLGA) NPs, using an innovative toroidal microfluidic system, for cancer therapy. The toroidal microfluidic system enabled the production of spherical NPs ranging from 100 to 150 nm by adjusting both the TFR within the range of 5–15 mL/min and FRR between 1:3 to 1:7. A systematic assessment of critical process variables (total flow rate; TFR, flow rate ratio; FRR) for the production of PLGA NPs was conducted using Design of Experiment (DoE). The NPs, which exhibit a uniform size distribution, remained stable even after centrifugation and storage for 3 months at 4 °C. The encapsulation efficiency of drug and the concentration of NPs were not affected by changing process parameters. The effective 5-FU encapsulation into NPs resulted in a controlled in vitro drug release. Due to the controlled release profile of the 5-FU loaded PLGA NPs, the formulation was a promising candidate for mitigating the toxic side effects of free 5FU and improving cancer treatment. In conclusion, toroidal microfluidic system enables high-volume production of stable PLGA NPs, both with and without 5-FU.

Unveiling the mucilage complexity in a multispecies exploration of the genus Alcea from Iran

Eight field-grown Alcea species (A. koelzii, A. kurdica, A. lavateriflora, A. rechingeri, A. remotiflora, A. rufescenc, A. schiraziana and A. tehranica) were analyzed for their mucilage content to identify the species with the highest yield. The mucilage was extracted with boiling water, precipitated by methanol, and subjected to acid hydrolysis by trifluoroacetic acid. Although mucilage content varied across Alcea species, root yields generally exceeded flower yields, with A. rechingeri roots reaching up to 26.43 %. HPLC analysis showed glucose as the dominant monosaccharide in root mucilage across all species. Rhamnose and fructose content, however, exhibited variations among the species. Field emission scanning electron microscopy micrographs showed layered or fibrous structures, while Fourier Transform Infrared Spectroscopy analysis confirmed a polysaccharide-based composition for flower and root mucilage. Energy dispersive X-ray analysis detected calcium, phosphorus, and magnesium, with higher concentrations in flower mucilage. X-Ray diffraction analysis confirmed the presence of both amorphous and semi-crystalline regions within the mucilage samples, with crystalline phases identified as calcium oxalate hydrate, alpha-cyclodextrin, and glutamic acid. In conclusion, A. koelzii flowers and A. rechingeri roots yielded the highest mucilage content, suggesting Alcea as a promising source of polysaccharides with potential applications in the pharmaceutical and food industries.

Deciphering the role and impact of India's pharmaceutical industries and its regulatory compliance

The pharmaceutical industry faces exceptionally high R&D costs, with the US research-based sector investing about 17% of sales into R&D. The cost of bringing a new compound to market was estimated at $802 million in 2001, up from $138 million in the 1970s and $318 million in the 1990s, necessitating stringent regulations. This study aims to determine the role and impact of India's pharmaceutical industry and its regulatory compliance. Personnel from organizations established between 1884 and 2004, with turnovers ranging from Rs. 25 crore (US $5.3 million) to Rs. 5500 crore (US $1.2 billion), were surveyed. Out of 150 companies approached, 73 responded, with 70 complete responses analyzed. Ongoing interactions with regulatory agencies helped companies better understand the regulatory system. Three key areas emerged as priorities: awareness of intellectual property rights (IPR) and patents, fostering a suitable environment for research and development, and implementing Good Manufacturing Practices (GMP), considered more critical than price control. The findings underscore the importance of regulatory compliance in promoting innovation and maintaining quality within the pharmaceutical industry, ensuring its competitiveness and ability to meet global standards.

Economics of Antibody Drug Conjugates (ADCs): Innovation, Investment and Market Dynamics.

This review aims to explore the intricate interplay between scientific advancements and economic considerations in the development, production, and commercialization of Antibody Drug Conjugates (ADCs). The focus is on understanding the challenges and opportunities at this unique intersection, highlighting how scientific innovation and economic dynamics mutually influence the trajectory of ADCs in the pharmaceutical landscape. There has been a significant increase in interest and investment in the development of ADCs. Initially focused on hematological malignancies, ADCs are now being researched for use in treating solid tumors as well. Pharmaceutical companies are heavily investing to broaden the range of indications for which ADCs can be effective. According to a report from the end of 2023, the global ADCs market grew from USD 1.4 billion in 2016 to USD 11.3 billion in 2023, with projections estimating a value of USD 23.9 billion by 2032, growing at a CAGR of 10.7%. ADCs represent a promising class of biopharmaceuticals in oncology, with expanding applications beyond hematological malignancies to solid tumors. The significant growth in the ADC market underscores the impact of scientific and economic factors on their development. This review provides valuable insights into how these factors drive innovation and commercialization, shaping the future of ADCs in cancer treatment.

Methionine aminopeptidases: Potential therapeutic target for microsporidia and other microbes.

Methionine aminopeptidases (MetAPs) have emerged as a target for medicinal chemists in the quest for novel therapeutic agents for treating cancer, obesity, and other disorders. Methionine aminopeptidase is a metalloenzyme with two structurally distinct forms in humans, MetAP-1 and MetAP-2. The MetAP2 inhibitor fumagillin, which was used as an amebicide in the 1950s, has been used for the successful treatment of microsporidiosis in humans; however, it is no longer commercially available. Despite significant efforts and investments by many pharmaceutical companies, no new MetAP inhibitors have been approved for the clinic. Several lead compounds have been designed and synthesized by researchers as potential inhibitors of MetAP and evaluated for their potential activity in a wide range of diseases. MetAP inhibitors such as fumagillin, TNP-470, beloranib, and reversible inhibitors and their analogs guide new prospects for MetAP inhibitor development in the ongoing quest for new pharmacological indications. This perspective provides insights into recent advances related to MetAP, as a potential therapeutic target in drug discovery, bioactive small molecule MetAP2 inhibitors, and data on the role of MetAP-2 as a therapeutic target for microsporidiosis.

Recent approaches of regulatory perspectives for the registration of drugs in southern states in India

Recent approaches in regulatory perspectives for the registration of drugs in Southern states of India have been characterized by a focus on enhancing efficiency, transparency, and safety in the drug approval process. This involves the adoption of stringent regulatory frameworks aligned with international standards to ensure the quality, efficacy, and safety of pharmaceutical products. One significant development is the implementation of electronic submission systems for the registration of drugs, streamlining the application process and reducing administrative burdens for regulators and pharmaceutical companies. Additionally, there has been an emphasis on strengthening post-marketing surveillance mechanisms to monitor the safety and efficacy of drugs once they are in the market, enabling prompt identification and mitigation of potential risks or adverse reactions. Collaborative efforts between regulatory authorities, industry stakeholders, and healthcare professionals have also been encouraged to facilitate knowledge exchange and capacity building in regulatory compliance and pharmacovigilance. Overall, these recent approaches reflect a concerted effort to uphold public health standards and ensure access to safe and effective medications for the population of Southern states in India.

Regioselective Deacetylation in Nucleosides and Derivatives.

Nucleoside analogues are a promising class of natural compounds in the pharmaceutical industry, and many antiviral, antibacterial and anticancer drugs have been created through structural modification of nucleosides scaffold. Acyl protecting groups, especially the acetyl group, play an important role in the protection of hydroxy groups in nucleoside synthesis and modification; consequently, numerous methodologies have been put forth for the acetylation of free nucleosides. However, for nucleosides that contain different O- and N-based functionalities, selective deprotection of the acetyl group(s) in nucleosides has been studied little, despite its practical significance in simplifying the preparation of partially or differentially substituted nucleoside intermediates. In this mini-review, recent approaches for regioselective deacetylation in acetylated nucleosides and their analogues are summarized and evaluated. Different regioselectivities (primary ester, secondary ester, full de-O-acetylation, and de-N-acetylation) are summarized and discussed in each section.

Pulsed Electric Field-Assisted Extraction of Inulin from Ecuadorian Cabuya (Agave americana)

Inulin is a carbohydrate that belongs to fructans; due to its health benefits, it is widely used in the food and pharmaceutical industries. In this research, cabuya (Agave americana) was employed to obtain inulin by pulsed electric field-assisted extraction (PEFAE) and FTIR analysis confirmed its presence. The influence of PEFAE operating parameters, namely, electric field strength (1, 3 and 5 kV/cm), pulse duration (0.1, 0.2 and 0.5 ms), number of pulses (10,000, 20,000 and 40,000) and work cycle (20, 50 and 80%) on the permeabilization index and energy expenditure were tested. Also, once the operating conditions for PEFAE were set, the temperature for conventional extraction (CE) and PEFAE were defined by comparing extraction kinetics. The cabuya meristem slices were exposed to PEFAE to obtain extracts that were quantified, purified and concentrated. The inulin was isolated by fractional precipitation with ethanol to be characterized. The highest permeabilization index and the lowest energy consumption were reached at 5 kV/cm, 0.5 ms, 10,000 pulses and 20%. The same extraction yield and approximately the same amount of inulin were obtained by PEFAE at 60 °C compared to CE at 80 °C. Despite, the lower amount of inulin obtained by PEFAE in comparison to CE, its quality was better because it is mainly constituted of inulin of high average polymerization degree with more than 38 fructose units. In addition, TGA analyses showed that inulin obtained by PEFAE has a lower thermal degradation rate than the obtained by CE and to the standard.

Essential Oil Content, Composition and Free Radical Scavenging Activity from Different Plant Parts of Wild Sea Fennel (Crithmum maritimum L.) in Montenegro

This study was conducted to determine the sea fennel essential oil (SFEO) yield, composition, and antioxidant activity of leaves, stem, inflorescences, and umbels from seeds of wild sea fennel (SF) (Crithmum maritimum L.) from the Montenegro coast. The chemical composition of isolated essential oil was determined by GC/MS and GC/FID analyses. The antioxidant activity was determined using the DPPH assay. The maximum SFEO yield was found in umbels with seeds (4.77 mL/100 g p.m.). The leaves contained less EO (0.52 mL/100 g p.m.) than immature inflorescence (0.83 mL/100 g p.m.) The minimum EO content was found in the stem (0.08%). Twenty components were isolated from SFEO leaves, twenty-four from inflorescence, thirty-four components from the stem, and twenty-one components from umbels with seeds. Limonene (62.4–72.0%), γ-terpinene (9.5–14.0%), α-pinene (1.4–5.8%), and sabinene (1–6.5%) were found to be the main components of the SFEO from monoterpene hydrocarbons as dominant grouped components (86% to 98.1%). SF plant parts showed differences in chemical profiles, especially in specific and low-represented ingredients. (E)-anethole (4.4%), fenchone (0.5%), and trans-carveol (0.2%) were present only in umbel with seeds, while the β-longipipene (0.5%), (E)-caryophyllene (0.5%), and (2E)-decenal (0.2%) were found only in the stems. The degree of DPPH radical neutralization increased with incubation time. The SFEO isolated from the stems showed stronger antioxidant activity during the incubation times of 20 and 40 min (EC50 value of 5.30 mg/mL and 5.04 mg/mL, respectively) in comparison to the SFEO isolated from the other plant parts. The lowest antioxidant activity was obtained with the SFEO leaves (155.25 mg/mL and 58.30 mg/mL, respectively). This study indicates that SFEO possesses significant antioxidant activities and is animportant component in the food and pharmaceutical industries. It is important to preserve the existing gene pool and biodiversity with rational use SF for the extraction of high-quality essential oils.

Spectroscopy: Types, Principles And Clinical Uses

Spectroscopic techniques can be classified based on the types of ray, reaction between the material and the energy, the form of material used and the usages for which the assay is utilized. Several types of spectroscopies have been developed, but the most frequently-used spectrometer utilized for biochemical analyses include nuclear magnetic resonance (NMR), Raman spectroscopy, infrared spectroscopy, ultraviolet and visible spectroscopy, and atomic spectroscopy. This review highlights the main types of spectroscopies and their principle of action and other technical issue. Spectroscopic chemical analysis now plays a vital role in pharmaceutical manufacturing. It is used for medication identification and quality assessment, as well as detecting metal elements and compounds present in solid or water materials — not forgetting its significant value in medical diagnostics

Performance of the Supply Chain in Operational Excellence: A Field Study in Jordanian Pharmaceutical Companies

Performance of the Supply Chain in Operational Excellence: A Field Study in Jordanian Pharmaceutical Companies

The Early Access and the Potential Cost Savings by the Compassionate Use of Onco-haematological Drugs: Results from the Italian Study Compass-O.

Compassionate drug use (CDU) provides early access to not yet authorised medicines and is funded by pharmaceutical companies. The observational retrospective study Compass-O monitored the CDU of onco-haematological drugs, managed by seven Italian units for cytotoxic drug preparations (Unità Farmaci Antiblastici [UFA]), between 1 January, 2016 and 31 December, 2021. We aimed to evaluate the CDU of onco-haematological drugs managed by seven Italian UFA, between 2016 and 2021. The seven UFA provided anonymised data concerning CDU approved in the study period. The early access and potential cost savings for the National Health System (Servizio Sanitario Nazionale [SSN]) were analysed for CDU concerning drug-therapeutic indication combinations with complete data and reimbursed by SSN up to December 2023 (date of study execution), according to the executive decision of the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]). Both analyses distinguished solid/liquid tumours and categorised the combinations as innovative (fully/conditionally) or non-innovative based on AIFA assessments. Compass-O collected 783 CDU authorisations, with 572 (73.1%) analysable in terms of early access and cost savings. On average, early access amounted to 514 days and the total cost savings was €376,115,801. Compassionate drug use approvals involved mainly solid tumours (93.7% vs 6.3% for liquid tumours), and the combination of trastuzumab emtansine-breast cancer was the most dispensed (n = 73; early access = 426 days;potential cost savings: €610,388). Out of 572 CDU approvals, 200 (35%) were innovative drug-therapeutic indication combinations, with 598 days of early access and a total potential saving of €113,124,069. The study Compass-O showed a significant economic burden of CDU and a relevant need for early access, particularly for innovative drugs. However, there is currently no structured monitoring of CDU in Italy, suggesting the need for a national observatory, of which Compass-O can be the pilot phase.

Evolutionary game model and simulation analysis of multi-stakeholder behaviour for promoting Braille labelling on pharmaceutical packaging in China’s legal framework

This study investigates the factors influencing the lack of Braille-embossed labels in Chinese pharmaceutical product packaging. To this end, this study constructs an evolutionary game model of multi-participant behaviour in drug production regulation and conducts simulation based on the perspective of stakeholders in order to study the evolutionary steady state of regulatory authorities, pharmaceutical companies, and visually impaired individuals and the influence of each parameter variable on the choice of strategic behaviour of the participants. The simulation results show that in the legal framework of China, administrative penalties, the production subsidy rate, and the Basic Medical Insurance (BMI) reimbursement rate are the main drivers of the system’s evolution towards a steady state. Reduced costs of drugs with Braille-embossed packaging is a prerequisite for the visually impaired to purchase such drugs, and the key for the whole system to converge to a stable state therefore lies in the BMI reimbursement rate for drugs with Braille-embossed packaging. This paper suggests that the Chinese government should improve the law enforcement mechanism for the regulation of the production of drugs with Braille-embossed packaging; increase the type and intensity of administrative penalties as well as production subsidies, tax incentives, and compliance incentives for pharmaceutical companies; and provide higher BMI reimbursement rates for the visually impaired. The results of the study provide valuable insights to improve accessibility to drugs and build a barrier-free environment for ensuring medication safety in China and other developing countries.

Advances in the Synthesis and Physiological Metabolic Regulation of Nicotinamide Mononucleotide

Nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD+), is involved in the regulation of many physiological and metabolic reactions in the body. NMN can indirectly affect cellular metabolic pathways, DNA repair, and senescence, while also being essential for maintaining tissues and dynamic metabolic equilibria, promoting healthy aging. Therefore, NMN has found many applications in the food, pharmaceutical, and cosmetics industries. At present, NMN synthesis strategies mainly include chemical synthesis and biosynthesis. Despite its potential benefits, the commercial production of NMN by organic chemistry approaches faces environmental and safety problems. With the rapid development of synthetic biology, it has become possible to construct microbial cell factories to produce NMN in a cost-effective way. In this review, we summarize the chemical and biosynthetic strategies of NMN, offering an overview of the recent research progress on host selection, chassis cell optimization, mining of key enzymes, metabolic engineering, and adaptive fermentation strategies. In addition, we also review the advances in the role of NMN in aging, metabolic diseases, and neural function. This review provides comprehensive technical guidance for the efficient biosynthesis of NMN as well as a theoretical basis for its application in the fields of food, medicine, and cosmetics.

Novel Saccharomyces uvarum x Saccharomyces kudriavzevii synthetic hybrid with enhanced 2-phenylethanol production

BackgroundOver the last two decades, hybridization has been a powerful tool used to construct superior yeast for brewing and winemaking. Novel hybrids were primarily constructed using at least one Saccharomyces cerevisiae parent. However, little is known about hybrids used for other purposes, such as targeted flavor production, for example, 2-phenylethanol (2-PE). 2-PE, an aromatic compound widely utilised in the food, cosmetic, and pharmaceutical industries, presents challenges in biotechnological production due to its toxic nature. Consequently, to enhance productivity and tolerance to 2-PE, various strategies such as mutagenesis and genetic engineering are extensively explored to improved yeast strains. While biotechnological efforts have predominantly focused on S. cerevisiae for 2-PE production, other Saccharomyces species and their hybrids remain insufficiently described.ResultsTo address this gap, in this study, we analysed a new interspecies yeast hybrid, II/6, derived from S. uvarum and S. kudriavzevii parents, in terms of 2-PE bioconversion and resistance to its high concentration, comparing it with the parental strains. Two known media for 2-PE biotransformation and three different temperatures were used during this study to determine optimal conditions. In 72 h batch cultures, the II/6 hybrid achieved a maximum of 2.36 ± 0.03 g/L 2-PE, which was 2–20 times higher than the productivity of the parental strains. Our interest lay not only in determining whether the hybrid improved in productivity but also in assessing whether its susceptibility to high 2-PE titers was also mitigated. The results showed that the hybrid exhibited significantly greater resistance to the toxic product than the original strains.ConclusionsThe conducted experiments have confirmed that hybridization is a promising method for modifying yeast strains. As a result, both 2-PE production yield and tolerance to its inhibitory effects can be increased. Furthermore, this strategy allows for the acquisition of non-GMO strains, alleviating concerns related to additional legislative requirements or consumer acceptance issues for producers. The findings obtained have the potential to contribute to the development of practical solutions in the future.